With an increase in the population of aged people, various diseases of circulation systems, particularly cerebral and cardiac circulation system diseases caused by atheroclerosis, hypertension, etc. have become a serious social problem. As the therapeutic medicines for such diseases, useful medicaments are those which have hyperkinemic actions, particularly those which exhibit vasodilating actions on cerebral blood vessels and coronary blood vessels, or those which have diuretic actions.
Also, in recent years, better use have been made of the medicaments which have anti-platelet aggregation actions for the treatment of thrombotic diseases. Furthermore, in view of the fact that leucotrienes which are metabolically produced by 5-lipoxygenase on arachidonic acid cascade possess potent coronary vasospasm, attention has been paid to the relationship between cardiac diseases such as angina pectoris and leukotrienes. Therefore it is said that the compounds which have 5-lipoxygenase-inhibitory actions are of use for the treatment of such circulatory diseases.
In U.S. Pat. No. 2852527 and Journal of Medicinal Chemistry, vol. 10, p. 264 (1967), there are described lower alkyl esters of 2-lower alkyl-5-hydroxy-4-tertiary-aminoindole-3-carboxylic acids which have central nervous system-stimulating actions and hypoglycemic actions.
However, the forementioned known compounds have high toxicity, and there has not been any suggestion about pharmacological actions against circulatory diseases.
In the specification of U.S. Pat. No. 4581355, there are disclosed some species of indole-3-carboxamide compounds, which have 5-lipoxygenase actions, antihypertensive actions or cardiac actions, but these compounds do not exhibit any diuretic actions.